Melatonin, a naturally occurring molecule, is produced by the pineal gland in a circadian manner to regulate biologic rhythms in humans. Recent studies report that
melatonin may be an attractive candidate as an
anticancer agent or for combined
therapy because of its
antioxidant, oncostatic and immunoregulatory activities. In this study, the potentiating effect of
melatonin was evaluated on the apoptosis induced by
puromycin as an anticancer drug in
acute promyelocytic leukemia HL-60 cells.
Melatonin did not show significant cytotoxicity against HL-60 cells compared to
puromycin. However,
melatonin significantly augmented the cytotoxicity of
puromycin. Consistently, combined treatment of
melatonin and
puromycin reduced the expression of
anti-apoptotic proteins, such as bcl-2 and bcl-x(L) , and also induced
caspase-3 activation and
poly (ADP-ribose) polymerase (PARP) cleavage compared to
puromycin treatment alone. Furthermore, cell cycle analysis revealed that
melatonin promoted
puromycin-induced apoptosis by increasing the sub-G1 population, but suppressing G2/M arrest in HL-60 cells. Interestingly,
melatonin activated the phosphorylation of 5'-adenosine monophosphate-activated
kinase (AMPK) in combination with
puromycin. Taken together, our results suggest that
melatonin potentiates
puromycin-induced apoptosis with
caspase-3 and AMPK activation in HL-60 cells, and thus,
melatonin treatment can be effectively applied to
leukemia treatment as a potential sensitizer for chemotherapeutic agents.